Hematocrit is the volume of red blood cells (RBC) expressed as a percentage of the volume of RBC in a whole blood sample. The normal hematocrit range for a typical human being is about 40 Vol. % to about 45 Vol. %. In extreme cases, the hematocrit range for a human beings can range from about 20 Vol. % to about 60 Vol. %.
Prior methods for estimating the hematocrit value of a blood sample have been based upon physical and/or chemical properties of the whole blood sample based upon the amount of red blood cells in the whole blood sample. For example, the hematocrit value of a whole blood sample has been estimated by measuring the RBC volume after centrifugation by conductivity, resistivity, impedance, and/or concentration of markers such as Na+ cations in red blood cells or heme concentration in hemoglobin and other properties which may be distinguished based on the amount of RBC in whole blood samples. Although hematocrit values of whole blood samples have been measured routinely in the clinical or laboratory setting, hematocrit values are not commonly measured with glucose-monitoring products such as home meters.
One device that may be used to determine the hematocrit value of a whole blood sample in glucose-monitoring products or systems is a biosensor or biosensor reagent. The dependence or sensitivity of a biosensor reagent to hematocrit is one factor used to determine the accuracy and quality of a glucose-monitoring product as the hematocrit level of a blood sample can impact the glucose level of the blood sample being tested.
One problem with using current biosensor reagents to determine the hematocrit value and, consequently, the glucose value of a whole blood sample involves RBC interference. Red blood cells are small particles in blood samples that block a biosensor reagent's ability to measure the glucose level of the blood sample. RBC interference contributes to a bias reading or a glucose bias in the biosensor reagents of glucose-monitoring products.
For a given sample of whole blood, the measurement of the percent glucose in a blood sample should not vary whether the sample is tested at a level of 20 Vol. % hematocrit or a level of 60 Vol. % hematocrit. However, due to RBC interference, there is a percentage bias in the glucose reading that is detected by the biosensor reagent that varies based upon the level of hematocrit in the sample. The bias reading caused by the hematocrit content of a blood sample is commonly referred to as “hematocrit effect.”
It is common for glucose biosensor reagents in glucose-monitoring products to exhibit hematocrit effect. For example, in some current glucose-monitoring products, the glucose assay bias for approximately 20 Vol. % RBC in whole blood to approximately 60 Vol. % RBC in whole blood generally ranges from about 15 Vol. % to about 20 Vol. %. In general, the higher the glucose bias, the less accurate the glucose reading and the worse the performance of the glucose-monitoring product. In contrast, the lower the glucose bias, the more accurate the glucose reading and the better the performance of the glucose-monitoring product.
The bias reading caused by the hematocrit content of a blood sample can have an adverse effect on patients. Patients who have low hematocrit levels may misinterpret their glucose value as being too high because of the glucose bias and think they need insulin to bring their high glucose level, down. Because the actual glucose level is not as high as the perceived glucose level, patients may drop their glucose level too low by unnecessarily taking too much insulin. Conversely, patients who have high hematocrit levels may misinterpret their glucose value as being normal when it is actually high because of the glucose bias. Because the actual glucose level is not as low as the perceived glucose level, patients may consistently forego or miss needed treatment, leading to long term medical complications.
One method for determining the glucose bias of a glucose biosensor reagent in a glucose-monitoring product is to measure the glucose value of the blood sample (Glum) using a glucometer and determine the reference value of the glucose content (Gluref). The value for Glum may be measured on a glucose-monitoring product such as a home meter. The value for Gluref is determined independently of the glucose-monitoring product using a reference method and a reference instrument. Gluref is typically determined in a clinical or laboratory setting. The percentage of glucose bias can be determined according to the relationship set forth in Equation 1:(Glum−Gluref)*100/Gluref  (Eq. 1)Determining the percentage of glucose bias using this method is only practical if the value for Gluref can be measured for every blood sample, but this is typically not feasible for users of glucose-monitoring products. In addition, this method of determining the percentage of glucose bias is inconvenient as the value for Gluref is measured in a clinical or laboratory setting.
There is, therefore, a need for methods for correcting and minimizing the glucose bias in glucose-monitoring products which is caused by the hematocrit effect. There is also a need for methods for correcting the glucose bias, if any, in glucose monitoring products such as home meters without the need for patient samples to be brought to a clinical or laboratory setting. There is also a need for devices which can perform such adjustments without the need for patients to bring blood samples to a clinician or laboratory for determining the glucose bias of the biosensor reagent.